Fecho K, Maslonek K A, Dykstra L A, Lysle D T
Department of Pharmacology, University of North Carolina at Chapel Hill, USA.
J Pharmacol Exp Ther. 1996 Feb;276(2):626-36.
The present study assessed the involvement of opioid receptors both in the central nervous system (CNS) and in the periphery (i.e., on immunocytes) in the immune alterations produced by acute morphine treatment in rats. The first experiment showed that the in vitro suppressive effects of morphine on the mitogen-stimulated proliferation of splenic and blood lymphocytes are produced only by a very high concentration of morphine and are not naltrexone-reversible. These results suggest that the in vitro immunomodulatory effects of morphine are not mediated by classical opioid receptors on immunocytes. A second experiment showed that s.c. doses of N-methylnaltrexone that do not gain access to the CNS, as determined by the tail-withdrawal assay, do not antagonize the suppressive effects of a single, s.c. injection of morphine on the mitogen-stimulated proliferation of splenic and blood lymphocytes, splenic natural killer cell activity and the production of interferon-gamma by stimulated splenocytes. Only a high s.c. dose of N-methylnaltrexone that does gain access to the CNS, as determined by the tail-withdrawal assay, blocks morphine's immunomodulatory effects. A third experiment demonstrated that N-methylnaltrexone is 4 to 5 log units more potent in antagonizing most of the immune alterations produced by a single, s.c. injection of morphine when administered i.c.v. than s.c. Taken together, the results of the present study strongly suggest that CNS opioid receptors play an important role in the immune alterations produced by acute morphine treatment in rats.
本研究评估了阿片受体在大鼠急性吗啡处理所产生的免疫改变中，在中枢神经系统（CNS）和外周（即免疫细胞上）的参与情况。第一个实验表明，吗啡对脾和血液淋巴细胞有丝分裂原刺激增殖的体外抑制作用仅由非常高浓度的吗啡产生，且不可被纳曲酮逆转。这些结果表明，吗啡的体外免疫调节作用不是由免疫细胞上的经典阿片受体介导的。第二个实验表明，通过甩尾试验确定不能进入中枢神经系统的皮下注射N-甲基纳曲酮剂量，不能拮抗单次皮下注射吗啡对脾和血液淋巴细胞有丝分裂原刺激增殖、脾自然杀伤细胞活性以及刺激的脾细胞产生γ-干扰素的抑制作用。只有通过甩尾试验确定能进入中枢神经系统的高皮下剂量N-甲基纳曲酮才能阻断吗啡的免疫调节作用。第三个实验证明，当脑室内给药时，N-甲基纳曲酮拮抗单次皮下注射吗啡所产生的大多数免疫改变的效力比皮下给药高4至5个对数单位。综合来看，本研究结果强烈表明，中枢神经系统阿片受体在大鼠急性吗啡处理所产生的免疫改变中起重要作用。
